In order to evaluate the information necessary for the stability and specificity of peptide-protein interactions in terms of noncovalent contacts and conformational flexibility, a model ribonuclease-S-(1-15) peptide was synthesized by solid phase technique. The amino acid sequence of this model peptide is polyalanine with a few incorporated residues of the native ribonuclease sequence that are predicted to provide critical contacts for the stability of the complex, and one catalytically essential component, His 12. However, the amino acid sequence of the model peptide is largely altered, the purified model peptide, as expected, formed a catalytically active noncovalent complex (36% of native) with ribonuclease-(21-124), confirming the necessity of the incorporated native amino acid residues in a helix for the formation of stable noncovalent complexes. Of the conserved amino acid residues, the functional roles of Phe-8 and His-12 were examined closely by high resolution carbon 13 NMR and X-ray crystallography. The participation of His-12 in the RNase-S catalytic mechanism was investigated by pH dependent catalytic activity of (4-F-His 12)SRNase-S. Conformational equivalence of the above complex with native complex is now being studied by crystallography by Dr. David Richardson of Duke University.